QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online January 26, 2007
doi: 10.1242/10.1242/dev.02772

This Article Summary Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Nathans, J. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Nathans, J.

Tissue/planar cell polarity in vertebrates: new insights and new questions

¹ Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Departments of Neuroscience and Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

View larger version (60K): [in this window] [in a new window]   Fig. 1. PCP phenotype in the Drosophila eye and wing, and subcellular localization of PCP proteins in wing epithelial cells. (A) A WT eye. (B) Vang mutant eye. The left panels show the arrangement of individual photoreceptor rhabdomeres (the central grey or black circular structures within each ommatidium). The right panels are schematics of the chirality and orientation of each ommatidium (black or red arrows for the different chiralities; green for nonchiral) and of the equator separating the two territories of differing chirality. In the Vang mutant eye, the ommatidia show defects in both chirality and rotation. (C) WT wing showing the nearly parallel alignment of distally pointing wing hairs. (D) Vang mutant wing showing aberrant wing hair orientations globally, but substantial alignment locally. Arrow indicates proximal (P) and distal (D); anterior is up. (E) The subcellular localization of PCP proteins in the Drosophila wing epithelium (Adler, 2002; Strutt, 2002; Klein and Mlodzik, 2005; Strutt and Strutt, 2005). Four adjacent hexagonal wing epithelial cells are shown, with PCP protein accumulation at proximal or distal faces coded in red or green, respectively. A-D reproduced with permission from Jenny and Mlodzik (Jenny and Mlodzik, 2006). Dgo, Diego; Ds, Dachsous; Dsh, Dishevelled; Fz, Frizzled; Pk, Prickle; Vang/Stbm, Van Gogh/Strabismus; Stan/Fmi, Starry night/Flamingo.

View larger version (73K): [in this window] [in a new window]   Fig. 2. Mouse planar cell polarity phenotypes. (A) Fully open neural tube (craniorrhachischisis) in a Fz3-/-;Fz6-/- fetus at embryonic day (E) 18. (B) Open eyelids in a Fz3-/-;Fz6-/- fetus at E18, shown by phalloidin staining of the anterior two-thirds of the eye; the edges of the eyelids are indicated by white arrows. (C) Hair follicle orientation defects on the dorsal surface of the Fz6-/- paw at postnatal day (P) 8. Proximal (left) and distal (right). The bases of the central digits are immediately beyond the right edge of each image. (D) Defects in inner ear sensory hair bundle orientation at E18 in a Vangl2 mutant (Lp/Lp), organ of Corti flat mount. Top, actin-rich stereocilia are labeled with phalloidin (red) and kinocilia are labeled with anti-acetylated tubulin (green). Bottom, diagrams of hair bundle orientations for each image. IHC, inner hair cells; OHC1, inner row of outer hair cells; OHC2, central row of outer hair cells; OHC3, outer row of outer hair cells. Reproduced with permission from Wang et al. (Wang et al., 2006b).

View larger version (22K): [in this window] [in a new window]   Fig. 3. The mammalian inner ear. (A) Location and architecture of sensory structures. (a) The structures of the bony labyrinth of the inner ear showing the locations of the cross-sectional views beneath. (b) Cross-sections through the main types of sensory epithelia, showing sensory hair cells. (c) Face-on views of these sensory epithelia, showing the apical face of the sensory hair cells and the arrangement of hair bundles. Left to right: crista (the sensory epithelium in the ampulla of each semicircular canal), utricle, and organ of Corti (the sensory structure in the cochlea). The saccule (not shown) closely resembles the utricle, except that its hair bundles face away from each other rather than towards each other across the equator (Denman-Johnson and Forge, 1999). In the ampulla of the semicircular canals, the tips of the sensory hair bundles on the apical face of each hair cell insert into a gelatinous structure called the cupula; in the utricle and saccule, sensory hair bundles insert into a gelatinous structure filled with calcium carbonate crystals, the otoliths; and in the organ of Corti, sensory hair bundles insert into the overlying tectorial membrane. Organ of Corti hair cells are arranged in four rows: one of inner (IHC) and three of outer (OHC) hair cells. In c, each kinocilium (black circle) lies adjacent to a group of stereocila (structures filled with actin bundles). In this view, the stereocilia form a V shape on the apical face of hair cells in the organ of Corti and a disc in the utricle, saccule and cristae. (B) Schematic of individual hair cells from the auditory system (a) and vestibular system (b). The apical face is at the top and the single kinocilium at the left edge. Panel A is reproduced with permission from Wang et al. (Wang et al., 2006b).

View larger version (93K): [in this window] [in a new window]   Fig. 4. Axon growth and guidance defects in the developing Fz3-/- and Celsr3-/- central nervous system. (A) Anti-neurofilament staining of horizontal sections through E15 WT and Fz3-/- mouse brains shows a complete absence of thalamocortical and corticothalamic fiber bundles in an otherwise normal-appearing Fz3-/- forebrain; the normal location of these fibers is indicated by an arrowhead. (B) DiI tracing of commissural axons in E11 WT and Celsr3-/- mouse spinal cords shows a failure of rostral turning by Celsr-/- axons after midline crossing. The spinal cord has been opened at the dorsal midline and flattened (an `open book' preparation). DiI was placed in commissural cell bodies beyond the left edge of each image. The vertical white line indicates the midline. A, Anterior/rostral; P, posterior/caudal. Panel A is reproduced with permission from Wang et al. (Wang et al., 2002) and panel B is courtesy of Drs Libing Zhou and Andre Goffinet.

View larger version (47K): [in this window] [in a new window]   Fig. 5. Hair follicle orientations on the back of WT and Fz6-/- mice at P0 and P4. (A-D) Posterior is to the right. The scatter plots show the angles of each hair follicle shaft (the region closest to the skin surface) and base (the region furthest from the skin surface) with respect to the anterior-posterior axis (set at zero degrees and corresponding to the central point along each axis). (A,B) WT follicles at P0 have orientations that range from -45 to +45 degrees, a distribution that narrows by P4. (C,D) Fz6-/- follicles at P0 have random orientations, which by P4 have partially reoriented to produce spatial domains with imperfect local order. Additional reorientation continues over the next several days (see Fig. 2C for follicle orientation at P8). In both WT and Fz6-/- skin, the distribution of shaft angles tightens more than that of bulb angles. Scale bar, 400 µm. Reproduced with permission from Wang et al. (Wang et al., 2006c).

View larger version (37K): [in this window] [in a new window]   Fig. 6. A two-dimensional lattice model of Fz6-/- hair follicle orientation development. Each hair follicle is represented by a unit length vector placed at one of the vertices of a lattice of equilateral triangles. After the initial vector orientations are set, the lattice develops by repeated application of an updating rule, which specifies that each vector's orientation becomes modified by adding to it the vector sum of its 18 closest neighbors after that sum has been scaled to 2% of its magnitude. This number of neighbors corresponds to two concentric circles of surrounding lattice points. The starting configuration (0) is a set of randomly oriented vectors, and the lattice is shown after 10, 20 and 100 iterations of the local consensus algorithm. Each vector orientation is represented by the angle and color of the corresponding bar, as shown in the key to the right. Reproduced with permission from Wang et al. (Wang et al., 2006c).

View larger version (113K): [in this window] [in a new window]   Fig. 7. Fz3 and Fz6 localization in mouse inner ear sensory epithelium. (A) Immunolocalization of Fz3 (green) in the organ of Corti at P0. Actin bundles are stained with phalloidin (red). IHC, inner hair cells; OHC1, inner row of outer HCs; OHC2, central row of outer HCs; OHC3, outer row of OHCs. (B) In the vestibular system, Fz6 (green) is expressed in supporting cells and sensory neurons. In the Fz3-/- crista, sensory hair bundle kinocilia orient to the right, as indicated by the hole on the actin-rich cuticular plate (phalloidin, red), which covers much of the apical face of the sensory neurons. Fz6 localizes preferentially on lateral faces that orient perpendicular to the axis of the sensory hair bundles. (C-E) WT:Fz6-/- mouse embryo chimeras and Fz6 protein localization. (C,D) Organ of Corti from a WT:Fz6-/- embryo chimera immunostained with anti-Fz6 (red) and anti-ß-galactosidase (green) to visualize nuclear ß-galactosidase encoded by Fz6-/- (lacZ knock-in) cells (asterisks). Phalloidin (blue) stains actin bundles. ß-galactosidase expression varies among Fz6-/- cells. The nuclei (D) are present in a deeper plane than the apical edge of the cells, where Fz6 accumulates (A). (E) An enlargement of the right corner of C, showing Fz6 punctate intracellular accumulation only in WT cells. Reproduced with permission from Wang et al. (Wang et al., 2006b).